Effect of quaternary ammonium surfactants on biomembranes using molecular dynamics simulation

Research conducted both prior to and after the emergence of the COVID-19 pandemic reveals a notable rise in human exposure to cleaning products, hand sanitizers, and personal care items. Moreover, there has been a corresponding increase in the environmental release of these chemicals. Cleaning and disinfecting products often contain quaternary ammonium compounds (QACs) with alkyl chains as long as 8–12 carbon atoms. The attachment of quaternary ammonium surfactants to the membrane resulted in the deformation of the bilayer and membrane disruption. Before interactions with cell membranes, these surfactant molecules may form different aggregates depending on their architecture. Interaction of surfactant monomers or clusters with the cell membrane changes the physiochemical properties of the biomembranes. To investigate this interaction and its influence on membrane properties, we conducted molecular dynamics simulations of cationic quaternary ammonium surfactants interacting with dipalmitoylphosphatidylcholine (DPPC) membranes. Our simulations revealed significant interactions between the surfactants and the phospholipids, leading to substantial alterations in the structure of the bilayer. The results are compared with the simulated anionic (SDS) and nonionic surfactants/bilayer systems. Various aspects were considered, including the aggregation process, migration behavior, and eventual equilibrium of these molecules at the interface between the membrane and water. This analysis used various techniques such as density profiles, distribution functions, cluster analysis, order parameters, hydrogen bonding (H-bonding), and mean-square displacements. The results indicate that while surfactants with shorter alkyl tails (N-(2-hydroxyethyl)-N,N-dimethyloctan-1-aminium chloride (HEDMOAC)) make strong hydrogen bonds with the phosphate group and ester oxygen of the phosphatidylcholine bilayer and enter toward the bilayer in the monomer form, surfactants of longer alkyl tails aggregated on the membrane head-water interface and interact minimally with the head groups of the DPPC bilayer. For DDEDMEAC, a quaternary ammonium surfactant with a hydrophobic alkyl chain consisting of two decanoate groups, alteration of the structural and dynamical properties of the bilayer is expected to be governed by two different factors. First, the structural order of DPPC increases as surfactant aggregates interact with the membrane head group. Second, the decrease in the order of the bilayer occurs due to the insertion of surfactant monomers within the hydrophobic region of the bilayer. Strong interactions between constituents of tetraoctylammonium bromide (TOABr) and lipid head groups lead to a reduction in interlipid interactions and order, which further results in increased porosity of cellular membranes. Understanding the extent of these interactions plays a pivotal role in the toxicological assessment of these surfactants.


Fig. S2 .
Fig. S2.MD simulation sample snapshots of the distribution of HEDMOAC in DPPC/water after 200 ns of simulation.Water molecules are shown with blue lines.Tail and head groups of DPPC are represented in orange lines and green, blue and brown points, respectively.

Fig. S3 .
Fig. S3.MD simulation sample snapshots of the distribution of DDEDMEAC in DPPC/water after 200 ns of simulation.Water molecules are shown with blue lines.Tail and head groups of DPPC are represented in orange lines and green, blue and brown points, respectively.

Fig. S4 .
Fig. S4.MD simulation sample snapshots of the distribution of TOABr in DPPC/water after 200 ns of simulation.Water molecules are shown with blue lines.Tail and head groups of DPPC are represented in orange lines and green, blue and brown points, respectively.

Fig. S5 .
Fig. S5.MD simulation sample snapshots of the distribution of OMEO in DPPC/water after 200 ns of simulation.Water molecules are shown with blue lines.Tail and head groups of DPPC are represented in orange lines and green, blue and brown points, respectively.

Fig. S7
Fig. S7 Density profiles of specific atom/groups relative to the z-axis, perpendicular to the plane of the bilayer, exploited from the MD simulations performed at T = 310 K, for (A) DPPC/SDS (B) DPPC/HEDMOAC (C) DPPC/ DDEDMEAC (D) DPPC/TOABr and (E) DPPC/OMEO systems.

Fig. S8 .
Fig. S8.(A) Average deuterium order parameters obtained for the sn-1 (B) and sn-2 chains of DPPC over the 150 ns of the simulation for HEDMOAC system.The calculated values of the control system are also shown.

Fig. S9 .
Fig. S9.(A) Average deuterium order parameters obtained for the sn-1 (B) and sn-2 chains of DPPC over the 150 ns of the simulation for DDEDMEAC system.The calculated values of the control system are also shown.

Fig. S10 .
Fig. S10.(A) Average deuterium order parameters obtained for the sn-1 (B) and sn-2 chains of DPPC over the 150 ns of the simulation for TOABr system.The calculated values of the control system are also shown.

Fig. S11 .
Fig. S11.(A) Average deuterium order parameters obtained for the sn-1 (B) and sn-2 chains of DPPC over the 150 ns of the simulation for OMEO system.The calculated values of the control system are also shown.

Fig. S12 .
Fig. S12.Radial distribution functions of (A) OW with cation, anion and O30 of DDEDMEAC (B) cation with anion and tail of DDEDMEAC (C) cation and anion of DDEDMEAC with headgroups of DPPC and (D) O31 and tail of DDEDMEAC with headgroups and tail of DPPC.

Fig. S13 .
Fig. S13.Radial distribution functions of (A) OW with cation and anion of TOABr (B) cation with anion and tail of TOABr (C) cation, anion and tail TOABr with headgroups and tail of DPPC.

Fig. S14 .
Fig. S14.Radial distribution functions of (A) OW and HW with O1 and and O4 of OMEO (B) tail of OMEO (C) headgroups and tail of DPPC with O1, O4 and tail of OMEO.

Fig. S15
Fig. S15 Radial distribution functions of (A) OW with cation, anion, and O14 of HEDMOAC (B) cation with anion of HEDMOAC and tail of HEDMOAC (C) headgroups of DPPC with cation and anion of HEDMOAC (D) O14 of HEDMOAC with headgroups of DPPC and tail of DPPC with tail of HEDMOAC.

Fig. S18
Fig. S18 Radial distribution functions of (A) OW with cation and anion of SDS (B) cation with anion of SDS and tail of SDS (C) cation of SDS with O9, O10 and P8 of POPC and (D) tail of SDS with tail of POPC and headgrups of POPC with anion of SDS.

Fig
Fig. S19 (A) Snapshot of the bilayer system during MD simulations of SDS in DPPC/water after 50 ns of simulation.(B) Total density profiles of DPPC/SDS/water.

Fig
Fig.S20 (A) Average values of the simulated S CD in terms of the sn-1 (B) and sn-2 chains of lipid molecules in the DPPC model membrane over the 50 ns of the simulation for SDS system.The calculated values of the control system are also shown.

Table S1 .
Ab initio calculated partial atomic charges of SDS.

Table S2 .
Ab initio calculated partial atomic charges of TOABr.

Table S3 .
Ab initio calculated partial atomic charges of DDEDMEAC.

Table S4 .
Ab initio calculated partial atomic charges of HEDMOAC.

Table S5 .
Ab initio calculated partial atomic charges of OMEO.

Table S7 .
Average cluster Size [molecules]of surfactant molecules at water/bilayer interface.